DESCRIPTION: Loss of sight in glaucomatous optic neuropathy is due to the death of retinal ganglion cells (RGCs). Our long-term goal is to rescue dysfunctioning RGCs to prevent cell death in the early stages of glaucoma. The objective of this study is to define the relationship between RGC dysfunction and induced changes of the intraocular pressure (lOP), and that between RGC dysfunction and death over time. Our central hypothesis is that RGC dysfunction precedes RGC death and can be reversed by lowering the lOP. Our research team includes experts in glaucoma, visual electrophysiology, retinal imaging, and biophysics. Our clinical setting has a uniquely large population of glaucoma patients and older subjects at increased risk of glaucoma due to African-American and Hispanic ethnicity. The specific aims are 1) to test the hypothesis that RGC dysfunction is caused by lOP and can be reversed by lowering lOP, and 2) to test the hypothesis that RGC dysfunction is larger than RGC loss at any given time in the progression of glaucoma. Functional losses resulting from both RGC loss and dysfunction of viable RGCs will be measured with the pattern electroretinogram (PERG), and anatomic loss of RGCs will be measured with Optical Coherence Tomography (OCT3). Both measures are optimized to probe an equivalent number of neurons with comparable sensitivity. Hypotheses are supported by preliminary results showing that PERG deficits are improved by lOP-lowering treatments, and exacerbated by temporary lOP increases, and that PERG losses are relatively larger than OCT losses. This combined, innovative approach will yield a better understanding of the pathophysiological mechanisms involved in the progression of glaucoma. It is expected that this research will provide a rationale for the early treatment or prevention of glaucoma, and will develop a method to monitor the efficacy of treatment based on the amount of PERG improvement. Since blindness from glaucoma is steadily growing with increasing longevity, these results are expected to have a high potential impact on alleviating the health care burden in our country. [unreadable] [unreadable] [unreadable]